The overall objective is to define more clearly the role of insulin and cycic 3',5'-nucleotides in the regulation of leukocytes involved in inflammatory and immunologic responses. Genetically diabetic mice will be used to look for defects in cellular immune responses. The insulin sensitivity of mononuclear leukocyte and neutrophil functions will be investigated. The insulin sensitivity of lymph node cells involved in mixed lymphocyte reactions (MLR) will be examined. A one-way MLR, glucose uptake, glycogen turnover, and changes in sensitivity of hormone-induced increases in either cyclic AMP or cyclic GMP will be used to compare normal and diabetic cells. The insulin sensitivity of normal and diabetic cells will be assessed by the ability of insulin to inhibit epinephrine and prostaglandin E1-induced increases in cyclic AMP. The insulin responsiveness of macrophages, B lymphocytes and T lymphocytes will be individually examined to determine insulin sensitive mononuclear cell type(s). Neutrophil responsiveness to insulin will be studied using normal and juvenile diabetic patients. The responsiveness of normal and diabetic neutrophils will be compared by measuring hormone-induced changes in cycic AMP and cyclic GMP, glucose uptake, and glycogen turnover. Finally, the relationship of abnormal chemotaxis to other neutrophil defects will be studied using diabetic and atopic patients. The nonphagocytic release of neutrophil lysosomal enzymes will be tested to assess this neutrophil response in patients with a known chemotactic defect.